The results suggest that gp130 expressed in sensory nerves not only mediates chronic inflammatory pain, but also contributes significantly to complex interactions between immune cells, tumor cells, and nerves in the context of cancer-evoked pain. Moreover, we identify IL-6 activating gp130, Gab1/Gab2, PI3K, and PKC- and regulating TRPV1 as a key mechanism linking cytokine release to sensitization of pain-sensing nerves.